March 8, 2023

The most important ophthalmology research updates, delivered directly to you.
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In this week's issue

  • A prospective study finds dichoptic therapy to be non-inferior to patching in amblyopic children.
  • Deep learning was shown to help assess retinitis pigmentosa progression using ultra-widefield fundus autofluorescence images to estimate visual function.
  • Plasma exchange therapy improved visual outcomes in patients with optic neuritis of various etiologies.
  • A multi-center, randomized study did not support routine use of postoperative triamcinolone acetonide for surgical repair of open globe trauma.

Home based dichoptic treatment for amblyopia


Not all treatments are created equal, particularly when it comes to adherence in children! Amblyopia affects 1-5% of the population and occurs when vision unilaterally or bilaterally does not develop correctly during childhood. The conventional treatment is part-time monocular deprivation; however, due to low adherence, recurrent or residual amblyopia is commonly reported. Dichoptic therapy involves showing each eye a separate independent field of view. This study is the first randomized controlled trial to analyze the noninferiority or superiority of monocular patching therapy compared to dichoptic therapy. The dichoptic therapy was created with CureSight, glasses that had an eye tracker that separated streamed visual stimuli to each eye to provide two separate digital channels. This prospective randomized, masked, noninferiority trial contained 103 children from the ages of 4-9 with either mixed-mechanism or anisometropic small-angle strabismic amblyopia. Children were randomized into two arms: either dichoptic therapy 90 minutes/day, 5 days/week for 16 weeks with CureSight or patching 2 hours/day 7 days/week for 16 weeks. Stereoacuity and binocular visual acuity improved in both groups and was not significantly different between the two groups (P=0.76 and P=0.07). The CureSight group had higher adherence than the patching group (P=0.011). Overall, CureSight was found to be non-inferior to patching and higher adherence to this dichoptic treatment may provide a more successful alternative treatment. 

Utilizing artificial intelligence to estimate visual function in retinitis pigmentosa

JAMA Ophthalmology

AI for your eye? Oh my! Retinitis pigmentosa (RP) is an incurable, degenerative condition that causes reduced visual acuity and visual field constriction. Fundus autofluorescence (FAF) is an imaging modality in which the retinal pigment epithelium's hyperfluorescence suggests the presence of early stage RP,  while hypofluorescence indicates the progression of RP. Utilizing ultra-widefield imaging techniques, investigators were able to take photos of the fundus and examine visual function in RP with deep learning AI models. This retrospective, cross-sectional study utilized 1274 eyes of 695 patients with RP. Ultra-widefield images were taken with FAF, pseudocolor, and both FAF and pseudocolor, and 31 ensemble models were used to estimate mean deviation on the Humphrey field analyzer, central retinal sensitivity, and best-corrected visual acuity. Ultra-widefield FAF pictures were found to provide the most accurate visual acuity assessment when compared to tested visual function. Compared to direct testing, the standardized regression coefficients were 0.684 (mean deviation), 0.697 (central sensitivity), and 0.309 (visual acuity). Due to its noninvasive nature, ultra-widefield fundus autofluorescence imaging may be useful for assessing the remaining visual function in patients with RP. Of note, deep learning is currently unable to diagnose patients as the patterns of RP progression differ widely between patients.

Visual outcomes following plasma exchange for optic neuritis

American Journal of Ophthalmology

PLEX can be a powerful player in the prognosis of optic neuritis. In 1991, the Optic Neuritis Treatment Trial (ONTT), demonstrated that high dose intravenous methylprednisolone resulted in faster visual recovery than oral prednisone or placebo for optic neuritis, but did not change final visual outcomes. Since that time, new biomarkers of disease causing optic neuritis besides multiple sclerosis have been identified, including aquaporin-4 antibodies (AQP4-IgG) for neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Plasma exchange (PLEX) has been studied as a new treatment for severe demyelinating attacks causing optic neuritis. This international multicenter retrospective study evaluated the outcomes of 395 cases of optic neuritis following PLEX and compared outcomes to raw data from the ONTT. Causes of optic neuritis included: multiple sclerosis (27%), MOGAD (23%), AQP4-NMOSD (19%), seronegative-NMOSD (9%), idiopathic (21%), and other (1%). Median visual acuity (VA) at time of PLEX was count fingers, while median final VA was 20/25 with no differences among etiologies. In 20% of cases, the final VA was 20/200 or worse. Patients with poor outcomes were older (p=0.002), had worse VA at time of PLEX (p<0.001), and longer delay to PLEX (p<0.001). In comparison with the ONTT subset, a final VA of worse than 20/40 occurred in 12% PLEX-treated cases versus 33% from the ONTT treated with IV methylprednisolone alone (p=0.04). While older age and worse VA at onset are non-modifiable factors for worse outcomes, this study highlights the importance of prompt initiation of PLEX in select patients with optic neuritis. 

Adjunctive triamcinolone acetonide in eyes undergoing vitreoretinal surgery after open globe trauma

British Journal of Ophthalmology

Try and sit alone with triamcinolone - or maybe not? Retinal detachment is a common complication of open globe trauma (OGT), which may recur after surgical repair due to proliferative vitreoretinopathy (PVR). Preliminary studies have shown that administration of corticosteroids at time of surgical repair may improve pathologic inflammation and proliferation and prevent PVR development. In this multi-center trial, 280 patients who experienced full-thickness OGT were randomized to standard surgical care with or without postoperative steroid triamcinolone acetonide into the vitreous cavity and subtenon space. Throughout the 6-month follow-up period after vitrectomy, at least 10-letter ETDRS improvement in visual acuity (VA) was achieved in 43.4% of standard surgical care participants and in 46.9% of the triamcinolone adjunct participants, with no significant differences between groups. No differences were detected between groups regarding PVR re-detachment, number of operations, or quality of life at 6 months. Rate of stable, complete retinal reattachment was significantly lower in the treatment arm (51.6%) compared to the control arm (64.2%). Whether triamcinolone conferred negative effects is unclear, as the treatment arm may have had more severe disease at baseline. Nevertheless, the findings from this study did not support routine use of postoperative triamcinolone acetonide for surgical repair of OGT. Further studies are needed to identify adjunct treatments that will improve visual outcomes following OGT.


How much time is optimal between anesthetic injection and surgical incision?

Ophthalmic Plastic and Reconstructive Surgery

What time is the best time? The use of epinephrine in local anesthesia aims to induce vasoconstriction, which reduces bleeding and extends the anesthetic effect. Determining the best time lapse between administering the anesthetic and making a skin incision is crucial in achieving vasoconstriction and reducing bleeding. The authors evaluated the optimal time delay for skin incision in 9 subjects with upper blepharoplasty procedure after local injection of lidocaine (20mg/mL) and epinephrine (12.5 ug/mL). They then assessed the tissue hypoperfusion using laser speckle contrast imaging and oxygen level using optical spectroscopy at the sight of the injection, 2 mm from the injection, and 4 mm from the injection. They found that longer time was required to reach hypoperfusion with increasing distance from the site of injection. Since the maximum effect (35% of the original perfusion) was observed even after 115 seconds at the site of the injection, the authors concluded that waiting 2 minutes after injection is sufficient to ensure maximum hypoperfusion before the surgery. However, this study is limited in its small sample size and restricted generalizability, as well as the lack of epinephrine concentration and distances affecting the drug diffusion rate according to Fick’s law of diffusion. 

Lens Landmarks

Does prophylactic photocoagulation help central retinal vein occlusion (CRVO) outcomes? This phase 3 randomized control trial in 1995 analyzed patients who had CRVO within the last year and split them into Group N (181 patients with nonperfused CRVO with no neovascularization) and Group M (151 patients with 20/50 or worse visual acuity and macular edema secondary to CRVO). The primary outcome for Group N was regression of the development of neovascularization after prophylactic pan-retinal photocoagulation (PRP). The primary outcome for Group M was visual acuity after macular grid laser therapy at 3 years. 

Key Points:
  • Group N: Prophylactic PRP reduced proportion of patients who developed iris or angle neovascularization, but this difference was not statistically significant (35% vs. 20%, OR 0.6, P = 0.17) after adjusting for baseline characteristics
  • Group N: Iris and angle neovascularization was more successfully treated by PRP in patients who had not had prophylactic PRP (56% vs. 22%, OR 4.5, P = 0.02)
  • Group M: There was no statistically significant difference in visual acuity in those who received grid laser versus those who received no treatment at 3 years. 
Overall, the CVOS study is a landmark study because it did not support prophylactic photocoagulation being utilized for the treatment of CRVO. While treatment regimens have changed since the development of Anti-VEGF agents and improved clinical imaging (OCT), the CVOS remains one of the important foundational studies in the field.

Question of the Week

A 79-year old woman presented to the Neuro-Ophthalmology clinic with increasing difficulty moving her eyes in all directions for the past 2 years, although no vision changes were noted. She also has difficulty speaking and frequently stumbles, causing her to fall backwards. Histological examination of her brain tissue is shown:
Based on these findings, the clinical criteria to diagnose her condition include all of the following except:

A. Progressively worsening headaches 
B. Progressive akinetic-rigid syndrome starting after age 40
C. Progressive vertical supranuclear gaze palsy
D. Slowing of vertical saccades

Keep scrolling for answer or click here

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